Circadian control of brain glymphatic and lymphatic fluid flow
Circadian control of brain glymphatic and lymphatic fluid flow
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DOI：
10.1038/s41467-020-18115-2
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发表时间：
2020-09-02
影响因子：
16.6
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
--
作者：
Hablitz, Lauren M.;Pla, Virginia;Nedergaard, Maiken
胶质淋巴系统是血管周围空间的网络，其促进脑脊髓液（CSF）移动到大脑中并清除代谢废物。这种液体运输系统由定位于星形胶质细胞血管末端的水通道水通道蛋白4（AQP4）支持。胶质淋巴系统在睡眠期间更有效，但睡眠时间是否会促进胶质淋巴功能仍然未知。我们在这里显示胶质淋巴流入和清除表现出内源性的昼夜节律，在小鼠的中间休息阶段达到峰值。脑脊液从小脑延髓池到淋巴结的引流表现出与胶质淋巴流入相反的每日变化，表明CSF在整个动物中的分布取决于一天中的时间。AQP4的血管周围极化在静息期最高，AQP4的丢失消除了胶质淋巴流入和引流到淋巴结的昼夜差异。我们的结论是，CSF分布的昼夜节律控制和AQP4支持这种节奏。
The glymphatic system is a network of perivascular spaces that promotes movement of cerebrospinal fluid (CSF) into the brain and clearance of metabolic waste. This fluid transport system is supported by the water channel aquaporin-4 (AQP4) localized to vascular endfeet of astrocytes. The glymphatic system is more effective during sleep, but whether sleep timing promotes glymphatic function remains unknown. We here show glymphatic influx and clearance exhibit endogenous, circadian rhythms peaking during the mid-rest phase of mice. Drainage of CSF from the cisterna magna to the lymph nodes exhibits daily variation opposite to glymphatic influx, suggesting distribution of CSF throughout the animal depends on time-of-day. The perivascular polarization of AQP4 is highest during the rest phase and loss of AQP4 eliminates the day-night difference in both glymphatic influx and drainage to the lymph nodes. We conclude that CSF distribution is under circadian control and that AQP4 supports this rhythm.